Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients
1 Department of Immunology, Hospital Universitario Central de Asturias, Oviedo 33006, Spain
2 Mucosal Immunology Laboratory, Department of Paediatrics and Immunology-IBGM, University of Valladolid, Valladolid, Spain
3 Department of Gastroenterology and Internal Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
4 Department of Gastroenterology, Hospital Universitario Central de Asturias, Oviedo, Spain
5 Department of Paediatrics, Hospital Universitario Central de Asturias, Oviedo, Spain
6 Department of Immunology, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain
7 Fundación Renal “Iñigo Álvarez de Toledo”, Madrid, Spain
BMC Medicine 2014, 12:34 doi:10.1186/1741-7015-12-34Published: 25 February 2014
Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes.
We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies.
Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without.
The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones.